Novel score predicts 10-year TB risk in patient contacts

A novel risk score successfully predicted and stratified the 10-year tuberculosis risk for adult contacts of patients who already had the disease, according to findings from a prospective derivation and external validation cohort study.

“Contacts of people with tuberculosis are at high risk of also developing tuberculosis,” Matthew J. Saunders, MBChB, of the section of infectious diseases and immunity at Imperial College London, and colleagues wrote. “However, resources for contact investigation are often limited in national tuberculosis programs, and adult contacts are rarely prioritized and frequently do not complete screening or take preventive therapy.”

Researchers also pointed out that administration of tests for latent TB infection is often complicated.

“These factors lead to difficulties in assessing who has latent tuberculosis or, when infection is confirmed, who is at high risk of progression to disease and, therefore, most likely to benefit from preventive therapy.”

Saunders and colleagues developed a scoring system to predict TB risk for 2,017 contacts of 715 index cases in Ventanilla, Peru, from 2002 to 2006. All contacts were aged 15 years or older, and median follow-up was 10.7 years, lasting until February, 2016. The researchers identified TB risk factors for index cases, households and contacts of patients using a Cox proportional hazards model, stratifying contacts as being at low, medium or high risk for the disease. They then validated the score in an urban setting in Callao, Peru, in 2014 and 2015 (n = 1,910).

Nine percent (n = 178) of contacts developed TB during a cumulative 19,147 person-years of follow-up (incidence, 0.93 per 100 person-years; 95% CI, 0.8-1.08), the researchers reported. Risk factors for TB included previous tuberculosis, BMI, age, sustained exposure to an index case, the index case occurring in a male patient, indoor air pollution, previous TB among household members, lower community household socioeconomic position and living in a household with a low number of windows in each room.

The low-risk group had a 2.8% 10-year risk for TB (95% CI, 1.7-4.4), compared with 6.2% (95% CI, 4.8-8.1) in the medium-risk group and 20.6% (95% CI, 17.3-24.4) in the high-risk group, Saunders and colleagues wrote. Contacts who were classified as high risk (n = 535; 27%) accounted for 60% of TB cases during follow-up. Saunders and colleagues reported that the score predicted TB independently of index-case drug sensitivity and tuberculin skin tests.

In the external validation cohort, 3% (n = 65) of contacts developed TB during 3,771 person-years of follow-up, the researchers reported (incidence, 1.7 per 100 person-years; 95% CI, 1.4-2.2). The 2.5-year TB risk was 1.4% in the low-risk group (95% CI, 0.7-2.8), 3.9% in the medium-risk group (95% CI, 2.5-5.9) and 8.6% (95% CI, 5.9-12.6) in the high-risk group.

In an accompanying editorial, Anna M. Mandalakas, MD, of the department of pediatrics at Baylor College of Medicine, and Frank Cobelens, MD, PhD, of the Amsterdam Institute for Global Health and Development, wrote that “Saunders and colleagues eloquently demonstrate the usefulness of well-recognized risk factors to identify contact as risk in a region with medium tuberculosis incidence and low HIV prevalence.”

Mandalakas and Cobelens cautioned, however, that because the researchers performed 10 years of follow-up in only the derivation cohort, the conclusion that their score was predictive of TB risk for a decade or more “might have been made post hoc.” They also pointed out that a risk score would be unlikely to predict instances of reinfection.

“Nonetheless, Saunders and colleagues’ findings still suggest an important advance over existing approaches for risk stratification among adult contacts,” Cobelens and Mandalakas wrote. – by Andy Polhamus

Disclosure: Mandalakas and Cobelens report no relevant financial disclosures. The researchers report no relevant financial disclosures.